Communication in the brain: research collaboration uncovers a novel mechanism of altered information processing between neurons / Responsible is a distinct class of glial cells / Major relevance for learning and processing of sensory input / Publication in the prestigious journal PLoS Biology
Scientists at Johannes Gutenberg University Mainz (JGU) in Germany have discovered a new signal pathway in the brain that plays an important role in learning and the processing of sensory input. It was already known that distinct glial cells receive information from neurons. However, it was unknown that these same glial cells also transmit information to neurons.
Oligodendrocyte progenitor cells in the brain (OPC, green) influence synaptic signaling between neurones (red) integrated in the neuronal network.
source: Institute of Molecular Cell Biology, JGU
Model of the molecular signaling pathways between OPC (green), a subgroup of glial cells, and the neuronal network (grey). The release of a fragment of the glial NG2 protein by enhanced protease activity in the OPC is a central component (see 1), modulating the signal transduction at defined (excitatory) synapses of the neuronal network (see 2).
source: Institute of Molecular Cell Biology, JGU
The glia release a specific protein fragment that influences neuronal cross-talk, most likely by binding to the synaptic contacts that neurons use for communication. Disruption of this information flow from the glia results in changes in the neural network, for example during learning processes.
The team composed of Dr. Dominik Sakry, Dr. Angela Neitz, Professor Jacqueline Trotter, and Professor Thomas Mittmann unravelled the underlying mechanism, from the molecular and cellular level to the network and finally the resulting behavioral consequences. Their findings constitute major progress in understanding complex pathways of signal transmission in the brain.
In mammalian brains glial cells outnumber nerve cells, but their functions are still largely unelucidated. A group of glial cells, so-called oligodendrocyte precursor cells (OPC), develop into the oligodendrocytes which ensheathe neuronal axons with a protective myelin layer thus promoting the rapid transmission of signals along the axon. Interestingly, these OPCs are present as a stable proportion – some five to eight percent of all cells in all brain regions, including adult brains. The Mainz-based researchers decided to take a closer look at these OPCs.
In 2000 it was discovered that OPCs receive signals from the neural network via synaptic contacts that they make with neurons. "We have now discovered that the precursor cells do not only receive information via the synapses, but in their turn use these to transmit signals to adjacent nerve cells. They are thus an essential component of the network," explained Professor Jacqueline Trotter from the Institute of Molecular Cell Biology at Mainz University.
Classically, neurons have been considered as the major players in the brain. Over the past few years, however, increasing evidence has come to light that glial cells may play an equally important role. "Glial cells are enormously important for our brains and we have now elucidated in detail a novel important role for glia in signal transmission," explained Professor Thomas Mittmann of the JGU Institute of Physiology.
The chain of communication starts with signals traveling from the neurons to the OPCs across the synaptic cleft via the neurotransmitter glutamate. This results in a stimulation of the activity of a specific protease, the alpha-secretase ADAM 10 in OPCs, which acts on the NG2 protein expressed by the precursor cells releasing a NG2 fragment into the extracellular space, where it influences neighboring neuronal synapses. The neurons react to this in the form of altered electrical activity. "We can use patch-clamp techniques to hear, as it were, how the cells talk to one another," said Thomas Mittmann.
"The process starts with the reception of signals coming from the neurons by the OPCs. This means that the feedback to the neurons cannot be seen as separated from the signal reception," explained Dominik Sakry, joint first author of the study, describing the cascade of events. The role of NG2 in this process became apparent when the researchers removed the protein: neuronal synaptic function is altered, modifying learning and disrupting the processing of sensory input that manifests in the form of behavioral changes in test animals.
The evidence that the communication between the two cell types in the brain is not a one-way system but a complex mechanism involving feedback loops was obtained in a collaborative project involving physiologists and molecular biologists. Participating in the project at Mainz University were the Faculties of Biology and Medicine and the Focus Program Translational Neurosciences (FTN) in the form of platform technology provided by the Mouse Behavioral Unit (MBU). The project was additionally supported by two Mainz Collaborative Research Centers (CRC 1080 and CRC-TR 128) and involved participation of the Leibniz Institute for Neurobiology in Magdeburg. Scientists from seven countries participated in the study.
The evidence that the communication between the two cell types in the brain is not a one-way system but a complex mechanism involving feedback loops was obtained within a broad-based project in which both physiologists and molecular biologists collaborated. Participating in the project at Mainz University were the Faculties of Medicine and Biology, the Focus Program Translational Neurosciences (FTN) and its Mouse Behavior Unit (MBU) together with two Mainz Collaborative Research Centers (CRC 1080 and CRC-TR 128) and the Leibniz Institute for Neurobiology in Magdeburg. Scientists from seven countries took part in the study.
Dominik Sakry, Angela Neitz et al.
Oligodendrocyte Precursor Cells Modulate the Neuronal Network by Activity-Dependent Ectodomain Cleavage of Glial NG2
PLoS Biology 12(11): e1001993, 11 November 2014
Professor Dr. Jacqueline Trotter
Institute of Molecular Cell Biology
Faculty 10: Biology
Johannes Gutenberg University Mainz (JGU)
D 55099 Mainz, GERMANY
phone +49 6131 39-20263 oder 39-22879
fax +49 6131 39-23840
Professor Dr. Thomas Mittmann
Institute of Physiology
Mainz University Medical Center
D 55099 Mainz
phone +49 0613139-27261
fax +49 6131 39-25560
http://www.uni-mainz.de/presse/16582_ENG_HTML.php (Press release "Scientists at Mainz University decode mechanisms of cell orientation in the brain", 31 July 2013)
http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001993 - Article ;
http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001990 - Synopsis ;
http://www.uni-mainz.de/presse/16582_ENG_HTML.php - press release "Scientists at Mainz University decode mechanisms of cell orientation in the brain", 31 July 2013
Petra Giegerich | idw - Informationsdienst Wissenschaft
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy